VHrare study: Prevalence, clinical features and management of severe rare bleeding disorders in a large cohort.

INTRODUCTION: Rare bleeding disorders (RBD) constitute 5% of total hereditary bleeding disorders, although the number could be higher, due to the presence of undiagnosed asymptomatic patients. The objective of this study was to analyze the prevalence and characteristics of patients with severe RBDs in our area. MATERIAL AND METHODS: We analyzed the patients with RBD followed at a tertiary-level hospital between January 2014 and December 2021. RESULTS: A total of 101 patients were analyzed, with a median age at diagnosis of 27.67 years (range 0-89), of which 52.47% were male. The most frequent RBD in our population was FVII deficiency. Regarding the diagnostic reason, the most frequent cause was a preoperative test and only 14.8% reported bleeding symptoms at the time of diagnosis. A genetic study was carried out in 63.36% of patients and the most frequent mutation type found was finding a missense mutation. CONCLUSIONS: The distribution of RBDs in our centre is similar to the one reported in the literature. The majority of RBDs were diagnosed from a preoperative test and this allowed preventive treatment prior to invasive procedures to avoid bleeding complications. 83% of patients did not have a pathological bleeding phenotype according to ISTH-BAT.

A phase III randomised study comparing concomitant radiochemotherapy with cisplatin and docetaxel as induction versus consolidation treatment in patients with locally advanced unresectable non-small cell lung cancer.

OBJECTIVES: To assess if induction radiochemotherapy followed by consolidation chemotherapy (arm A) will improve survival in comparison with the same chemotherapy given as induction followed by consolidation concurrent radiochemotherapy (arm B) in patients with unresectable non-metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Chemotherapy consisted in a combination of cisplatin with docetaxel, with one initial course for each patient, two courses in single modality therapy and weekly administration during chest irradiation (66 Gy). RESULTS: A total of 125 patients were randomised before early closure of the study because of poor accrual and an unplanned blind interim analysis which suggested that the continuation of the study would have been futile. Mature survival results showed no significant difference between both modalities with median survival times, respectively in arms A and B, of 19.6 months and 18.3 months, two years survival rates of 44% and 44% and five years survival rates of 23% and 26%. Toxicity was acceptable. CONCLUSIONS: Our randomised study did not demonstrate survival difference between induction concurrent radiochemotherapy followed by consolidation chemotherapy and induction chemotherapy followed by consolidation concurrent radiochemotherapy.

Twelve years of experience with miglustat in the treatment of type 1 Gaucher disease: The Spanish ZAGAL project.

We report data from a prospective, observational study (ZAGAL) evaluating miglustat 100mg three times daily orally. in treatment-naïve patients and patients with type 1 Gaucher Disease (GD1) switched from previous enzyme replacement therapy (ERT). Clinical evolution, changes in organ size, blood counts, disease biomarkers, bone marrow infiltration (S-MRI), bone mineral density by broadband ultrasound densitometry (BMD), safety and tolerability annual reports were analysed. Between May 2004 and April 2016, 63 patients received miglustat therapy; 20 (32%) untreated and 43 (68%) switched. At the time of this report 39 patients (14 [36%] treatment-naïve; 25 [64%] switch) remain on miglustat. With over 12-year follow-up, hematologic counts, liver and spleen volumes remained stable. In total, 80% of patients achieved current GD1 therapeutic goals. Plasma chitotriosidase activity and CCL-18/PARC concentration showed a trend towards a slight increase. Reductions on S-MRI (p=0.042) with an increase in BMD (p<0.01) were registered. Gastrointestinal disturbances were reported in 25/63 (40%), causing miglustat suspension in 11/63 (17.5%) cases. Thirty-eight patients (60%) experienced a fine hand tremor and two a reversible peripheral neuropathy. Overall, miglustat was effective as a long-term therapy in mild to moderate naïve and ERT stabilized patients. No unexpected safety signals were identified during 12-years follow-up.

A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer.

INTRODUCTION: In a literature meta-analysis, we showed survival benefits for regimens including cisplatin [hazard ratio (HR) 0.61; 95% confidence interval (CI), 0.57-0.66] and for those including etoposide (HR 0.65; 0.61-0.69). That benefit was mainly observed when etoposide alone or in combination with cisplatin was included in the chemotherapy regimens. Our objective was to determine if chemotherapy with both drugs improves survival in comparison to a non-platinum regimen with etoposide. METHODS: Extensive small-cell lung cancer patients were randomized between cisplatin-etoposide (CE) and ifosfamide + etoposide + epirubicin regimen (IVE) between 2000 and 2013. RESULTS: 176 and 170 eligible patients were allocated to CE and IVE (315 deaths were required before analysis), respectively. Objective response rates were not significantly different: 60% with CE and 59% with IVE. No statistically significant difference in median survival and 1-year and 2-year was observed with rates of 9.6 months, 31 and 5% for CE and 10 months, 39 and 9% for IVE, respectively. HR was 0.84 (95% CI 0.68-1.05, p = 0.16). Only two prognostic factors for survival were retained in multivariate analysis: sex with HR = 0.69 (95% CI 0.49-0.97, p = 0.03) and performance status with HR = 0.53 (95% CI 0.49-0.97, p < 0.0001). After adjustment for these prognostic factors, HR for survival was 0.83 (95% CI 0.65-1.08, p = 0.17). There was more thrombopenia in the CE regimen and more leukopenia with IVE. CONCLUSION: Combination of CE failed to improve survival in comparison to an etoposide-containing regimen without cisplatin. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT00658580?term=ELCWP+01994&rank=1, identifier NCT00658580.

Intercalated Dosing Schedule of Erlotinib and Docetaxel as a Therapeutic Strategy to Avoid Antagonism and Optimize Its Benefits in Advanced Non-Small-Cell Lung Cancer. A Randomized Phase II Clinical Trial.

INTRODUCTION: The purpose of this study was to assess whether an intercalated dosing schedule of erlotinib and docetaxel could avoid possible negative interactions and optimize the benefit obtained as second-line therapy in non-small-cell lung cancer (NSCLC) patients. PATIENTS AND METHODS: A phase II randomized clinical trial was designed for advanced NSCLC patients in whom previous chemotherapy treatment had failed. The experimental arm with 33 patients consisted of erlotinib 150 mg/d orally, intermittent administration on days 2 to 16 every 21 days, combined with docetaxel 75 mg/m(2) every 21 days; the control arm with 35 patients consisted of erlotinib 150 mg/d orally, administered continuously. The study's primary end point was the proportion of patients who remained progression-free at 6 months in the 2 arms. RESULTS: The proportion of patients who remained progression-free at 6 months was of 5 patients (15%) in the intercalated arm and 3 patients (9%) in the erlotinib monotherapy arm respectively. Median progression-free survival (PFS) was 3.0 versus 2.1 months (hazard ratio [HR], 0.65; 95% confidence interval [CI], 0.39-1.06; P = .086). Median overall survival (OS) was 7.5 and 5.2 months (HR, 0.70; 95% CI, 0.41-1.19; P = .19). Disease control rates were 51.7% and 36.4%, respectively. No new safety signals were observed. CONCLUSION: Erlotinib and docetaxel with intermittent administration of erlotinib improved PFS, OS, and disease control rates compared with erlotinib alone. All of our results indicated that an intercalated dosing schedule of erlotinib and docetaxel could be more efficient than erlotinib treatment alone. Therefore, further studies should be developed in a larger number of patients. This study has shown the absence of antagonism between docetaxel and erlotinib when given in an intercalated fashion.

Full-dose cisplatin and oral vinorelbine concomitant with radiotherapy in unresectable stage III non-small cell lung cancer: a multi-center phase II study.

AIM: To evaluate the efficacy and toxicities of combination of cisplatin and oral vinorelbine given at full doses concomitantly with radiotherapy for non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Untreated patients with locally advanced inoperable stage IIIA/IIIB NSCLC were eligible for study inclusion. Treatment consisted of four cycles of oral vinorelbine at 60 mg/m(2) on days 1 and 8, and cisplatin at 80 mg/m(2) on day 1 every three weeks plus radiotherapy 66 Gy starting on day 1 of cycle 2 in fractions of 2 Gy/day over 6.5 weeks. RESULTS: Forty-eight patients were enrolled. Their characteristics included: median age 61 years; female gender 10%; stage IIIA 46% and IIIB 54%; squamous carcinoma 63%, performance status PS0 42%; PS1 58%. Selected grade 3/4 toxicities were as follows: neutropenia 33%, concomitant febrile neutropenia 14.6%, anemia 12.5%, thrombocytopenia 16.6%, and esophagitis 12.5%. Two treatment-related deaths were reported, both during cycle 1. Radiotherapy was administered to 87.5% of patients; 7.1% of them received less than 60 Gy and 23.8% had delays due to adverse events. The objective response rate was 77.3%, with two complete responses and 32 partial responses. With a median follow-up of 19 months, the median progression-free survival was 12 months, and the 1-year overall survival rate was 72.3%. Median overall survival was 27.8 months, although the 95% confidence interval has not yet been achieved. CONCLUSION: Full doses of cisplatin and oral vinorelbine can be administered with concomitant radiotherapy, with good efficacy and an acceptable safety profile for patients with stage IIIA/IIIB NSCLC.

[Evaluation of alignment on knees through a software]. / Evaluación de la alineación en rodillas mediante un software.

INTRODUCTION: Diseases of the musculoskeletal system are often accompanied by postural deformity or malalignment. Genu varo or genu valgo can be found in the knees. It is necessary to have a diagnostic support test for diagnosis as well as for follow-up of cases since these diseases are frequently progressive and over time have serious repercussions on patient quality of life. Objective. To evaluate a software program that processes digitalized photographs as a diagnostic test for measuring the mechanical axis in patients with genu varo and genu valgo. MATERIALS AND METHODS: The mechanical axis in both knees was measured by means of radiography (golden standard) and by means of a software program (proposed diagnostic test) in one hundred patients. Mechanical axis was considered to be abnormal when the angle was equal to or greater than four degrees. Sensitivity, specificity, positive predictive value, and negative predictive value were determined. Interobserver variation was evaluated with kappa statistics. RESULTS: In relation to right knee genu varo, sensitivity, specificity, positive predictive value, and negative predictivie value were 0.84, 0.87, 0.84, and 0.87, respectively, and for the left knee values were 0.86, 0.87, 0.84, and 0.89, respectively. For genu valgo in the right knee, sensitivity, specificity, positive predictive value, and negative predictive value were 0.78, 0.98, 0.95, and 0.92, respectively, and in the left knee were 0.88, 0.95, 0.88, and 0.95, respectively. Kappa value was 0.9 in the right knee and 0.8 in the left knee. CONCLUSION: The software program (diagnostic test) was useful for diagnosing genu varo or genu valgo, representing a safe and low-cost study.

The population-based prevalence of osteoporotic vertebral fracture and densitometric osteoporosis in postmenopausal women over 50 in Valencia, Spain (the FRAVO study).

PURPOSE: To estimate the prevalence of vertebral fracture and densitometric osteoporosis in postmenopausal women over the age of 50 in Valencia, Spain. METHODS: This cross-sectional study was conducted in 2006-2007. An age-stratified population-based random sample of 824 postmenopausal women over the age of 50 answered a questionnaire and received a densitometric examination of the lumbar spine and hip with dual-energy X-ray absorptiometry and a lateral X-ray of the thoracic spine and lumbar regions. Osteoporosis was defined as a T-score less than or equal to -2.5 compared to a population of young women, and the presence of vertebral fractures was classified according to Genant's semiquantitative method. RESULTS: The average age of the women was 64 years (range 50-87 years). The prevalence for all vertebral fractures was 21.4% (95% CI: 17.7%-25.1%) and 9.7% (95% CI: 6.7%-12.7%) for moderate-severe fractures. In women over the age of 75, the respective values were 46.3% (95% CI: 34.2%-58.3%) and 23.9% (95% CI:13.6%-34.2%). Only 1.5% of the women with vertebral fractures were aware of their condition. The prevalence of osteoporosis was estimated as 27.0% (95% CI:23.1%-30.8%) for the lumbar spine, 15.1% (95% CI:11.7%-18.5%) in the femoral neck, and 31.8% (95% CI:27.8%-35.7%) at either sites. CONCLUSIONS: The study confirms that osteoporosis (1 in 3 women over the age of 50) and vertebral fracture (1 in 5 for all fractures and 1 in 10 for moderate-severe fractures) constitute a major public health and healthcare challenge; measuring their real impact will depend in part on the criteria used to define a fracture.

Development and validation of a population-based prediction scale for osteoporotic fracture in the region of Valencia, Spain: the ESOSVAL-R study.

BACKGROUND: Today, while there are effective drugs that reduce the risk of osteoporotic fracture, yet there are no broadly accepted criteria that can be used to estimate risks and decide who should receive treatment. One of the actual priorities of clinical research is to develop a set of simple and readily-available clinical data that can be used in routine clinical practice to identify patients at high risk of bone fracture, and to establish thresholds for therapeutic interventions. Such a tool would have high impact on healthcare policies. The main objective of the ESOSVAL-R is to develop a risk prediction scale of osteoporotic fracture in adult population using data from the Region of Valencia, Spain. STUDY DESIGN: An observational, longitudinal, prospective cohort study, undertaken in the Region of Valencia, with an initial follow-up period of five years; SUBJECTS: 14,500 men and women over the age of 50, residing in the Region and receiving healthcare from centers where the ABUCASIS electronic clinical records system is implanted; SOURCES OF DATA: The ABUCASIS electronic clinical record system, complemented with hospital morbidity registers, hospital Accidents & Emergency records and the Regional Ministry of Health's mortality register; Measurement of results: Incident osteoporotic fracture (in the hip and/or major osteoporotic fracture) during the study's follow-up period. Independent variables include clinical data and complementary examinations; ANALYSIS: 1) Descriptive analysis of the cohorts' baseline data; 2) Upon completion of the follow-up period, analysis of the strength of association between the risk factors and the incidence of osteoporotic fracture using Cox's proportional hazards model; 3) Development and validation of a model to predict risk of osteoporotic fracture; the validated model will serve to develop a simplified scale that can be used during routine clinical visits. DISCUSSION: The ESOSVAL-R study will establish a prediction scale for osteoporotic fracture in Spanish adult population. This scale not only will constitute a useful prognostic tool, but also it will allow identifying intervention thresholds to support treatment decision-making in the Valencia setting, based mainly on the information registered in the electronic clinical records.

[Comparison of three therapeutic exercises protocols to lumbar hyperlordosis improvement in asyntomatic youths]. / Comparación de tres protocolos de ejercicios terapéuticos para corrección de la hiperlordosis lumbar en jóvenes asintomáticos.

INTRODUCTION: One of the causes of low back pain is lumbar hyperlordosis. There are different protocols of therapeutic exercises for its correction, which do not involve all of corporal segments. A modified protocol is proposed, which involves all such segments. OBJECTIVE: To evaluate the efficacy of proposed protocol with two established protocols for correction of lumbar hyperlordosis. MATERIALS AND METHODS: Simple-blind clinical trial on 42 students of the Faculty of Medicine at University of Colima. The three protocols: A) Pérez-Olmedo (proposed, n = 14), B) Williams (n = 15) and C) Jeffrey Saal (n = 13) were randomly assigned. Clinical and radiological evaluations were performed. Lumbar hyperlordosis was considered when Ferguson's angle was > or = 30 degrees, measured on lateral spine x-ray pictures. During two months they underwent supervised and directed exercise sessions. The improvement in lumbar hyperlordosis correction of each protocol was compared through paired Student t-test and ANOVA. RESULTS: Average age was 18 +/- 0.9 years. Lumbar hyperlordosis frequency was 31% (n = 15). There was not significative difference on Ferguson's angle average comparation between three treatment groups. There was lumbar hyperlordosis improvement with following percentages: group A = 60%, Group B = 16% and group C = 0%. CONCLUSION: Protocol of therapeutic exercises proposed (Pérez-Olmedo) could be an alternative to lumbar hyperlordosis improvement in asyntomatic youhts.

[Alternative method for measuring the mechanical axis of the knee]. / Método alterno para medición del eje mecánico de rodillas.

OBJECTIVE: To identify the existence of significant differences in the degrees of mal-alignment of the mechanical axis of the knee between a traditional measuring method and an alternative method. MATERIALS AND METHODS. One hundred mechanical axes of the knee were determined in patients of both sexes. The degree of axis mal-alignment was obtained first using the traditional measuring method and subsequently using the alternative method. The results obtained from the two methods were then compared. The measurement variable control was standardised by positioning the patients in the same place during radiography when beginning mechanical axis determination. A wooden ruler on which each centimetre was indicated by a metal strip and numbered at every 10-centimeter interval was used to evaluate the degree of pelvic mal-alignment. The ruler was then used as a mechanical axis correction reference in accordance with the characteristics of each patient. RESULTS: The following results were obtained from 100 mechanical axes evaluated by the traditional method and by the alternative method, respectively: varus deformity of the right pelvic segment was 21 degrees +/- 16 degreesuv. 7 ++/-6. degrees varus deformity of the left pelvic segment was 22 _+/-170 degreesvs. 8 ++/-50 degrees valgus deformity of the right pelvic segment was 21 - /-150 degreess. 8 + +/-; and valgus deformity of the left pelvic segment was 16 +/- 11 vs. 6 +/- 5 degrees. CONCLUSIONS: Our results suggest that the proposed method provides more accurate mechanical axis measurement and that the correction is exponential: the greater the angle measured traditionally, the greater the correction with our proposed method.

Fiebre prolongada por la ingesta de Hypericum perforatum (hierba de San Juan) / Persistent fever due to ingestion of Hypericum perforatum (St. John’s wort)

No disponible

Proteinuria persistente en mujer hipertensa infectada por el VIH / Persistent proteinuria in an HIV-infected hypertensive woman

No disponible

Inadequate cytoplasmic antioxidant enzymes response contributes to the oxidative stress in human hypertension.

Untreated hypertensive patients show increased oxidative stress and decreased antioxidant enzyme activity in mononuclear cells. Therefore, the objective of this study was to determine whether or not the low antioxidant enzyme activity observed in mononuclear cells of hypertensive subjects is in part dependent on a defective activity of antioxidant mechanisms. Activity and mRNA level of antioxidant enzymes, CuZn- and Mn-superoxide dismutases, catalase, glutathione peroxidase type 1, and glutathione reductase were simultaneously measured in mononuclear cells of controls (n = 38) and hypertensive subjects (n = 35), in the absence of and during antihypertensive treatment. An increase in oxidative stress and a decrease in the activity of cytoplasmic enzymes were observed in untreated hypertensive patients. Concurrently, CuZn-superoxide dismutase and glutathione reductase mRNA levels were significantly reduced, and glutathione peroxidase type 1 mRNA was slightly reduced. In contrast, increased activity and mRNA levels of the mitochondrial Mn-superoxide dismutase were observed. Antihypertensive treatment, nonpharmacologic with or without a drug regimen of beta-blocker or angiotensin AT1 receptor blocker was administered for a 3-month period. Afterward, after the improvement in oxidative stress during treatment, a recovery of the cytoplasmic antioxidant enzymatic activity and a more profound decrease in mRNA levels were observed for CuZn-superoxide dismutase, glutathione peroxidase type 1, and glutathione reductase. Meanwhile mitochondrial enzymatic activity decreased, as did the mRNA level. The inadequate response of the main cytoplasmatic antioxidant systems, as well as of the enzymes participating in the maintenance of glutathione levels, may contribute to the vulnerability of hypertensives to oxidative stress.